Prediction of post-radiotherapy recurrence volumes in head and neck squamous cell carcinoma using 3D U-Net segmentation

Locoregional recurrences (LRR) are still a frequent site of treatment failure for head and neck squamous cell carcinoma (HNSCC) patients. Identification of high risk subvolumes based on pretreatment imaging is key to biologically targeted radiation therapy. We investigated the extent to which a Convolutional neural network (CNN) is able to predict LRR volumes based on pre-treatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) scans in HNSCC patients and thus the potential to identify biological high risk volumes using CNNs. For 37 patients who had undergone primary radiotherapy for oropharyngeal squamous cell carcinoma, five oncologists contoured the relapse volumes on recurrence CT scans. Datasets of pre-treatment FDG-PET/CT, gross tumour volume (GTV) and contoured relapse for each of the patients were randomly divided into training (n=23), validation (n=7) and test (n=7) datasets. We compared a CNN trained from scratch, a pre-trained CNN, a SUVmax threshold approach, and using the GTV directly. The SUVmax threshold method included 5 out of the 7 relapse origin points within a volume of median 4.6 cubic centimetres (cc). Both the GTV contour and best CNN segmentations included the relapse origin 6 out of 7 times with median volumes of 28 and 18 cc respectively. The CNN included the same or greater number of relapse volume POs, with significantly smaller relapse volumes. Our novel findings indicate that CNNs may predict LRR, yet further work on dataset development is required to attain clinically useful prediction accuracy

SNPs and real-time quantitative PCR method for constitutional allelic copy number determination, the VPREB1 marker case

<p>Abstract</p> <p>Background</p> <p>22q11.2 microdeletion is responsible for the DiGeorge Syndrome, characterized by heart defects, psychiatric disorders, endocrine and immune alterations and a 1 in 4000 live birth prevalence. Real-time quantitative PCR (qPCR) approaches for allelic copy number determination have recently been investigated in 22q11.2 microdeletions detection. The qPCR method was performed for 22q11.2 microdeletions detection as a first-level screening approach in a genetically unknown series of patients with congenital heart defects. A technical issue related to the <it>VPREB1 </it>qPCR marker was pointed out.</p> <p>Methods</p> <p>A set of 100 unrelated Italian patients with congenital heart defects were tested for 22q11.2 microdeletions by a qPCR method using six different markers. Fluorescence In Situ Hybridization technique (FISH) was used for confirmation.</p> <p>Results</p> <p>qPCR identified six patients harbouring the 22q11.2 microdeletion, confirmed by FISH. The <it>VPREB1 </it>gene marker presented with a pattern consistent with hemideletion in one 3 Mb deleted patient, suggestive for a long distal deletion, and in additional five non-deleted patients. The long distal 22q11.2 deletion was not confirmed by Comparative Genomic Hybridization. Indeed, the <it>VPREB1 </it>gene marker generated false positive results in association with the rs1320 G/A SNP, a polymorphism localized within the <it>VPREB1 </it>marker reverse primer sequence. Patients heterozygous for rs1320 SNP, showed a qPCR profile consistent with the presence of a hemideletion.</p> <p>Conclusions</p> <p>Though the qPCR technique showed advantages as a screening approach in terms of cost and time, the <it>VPREB1 </it>marker case revealed that single nucleotide polymorphisms can interfere with qPCR data generating erroneous allelic copy number interpretations.</p

What you always needed to know about electroporation based DNA vaccines

Vaccinations are increasingly used to fight infectious disease, and DNA vaccines offer considerable advantages, including broader possibilities for vaccination and lack of need for cold storage. It has been amply demonstrated, that electroporation augments uptake of DNA in both skin and muscle, and it is foreseen that future DNA vaccination may to a large extent be coupled with and dependent upon electroporation based delivery. Understanding the basic science of electroporation and exploiting knowledge obtained on optimization of DNA electrotransfer to muscle and skin, may greatly augment efforts on vaccine development. The purpose of this review is to give a succinct but comprehensive overview of electroporation as a delivery modality including electrotransfer to skin and muscle. As well, this review will speculate and discuss future uses for this powerful electrotransfer technology

Change in Hemoglobin Levels due to Anesthesia in Mice: An Important Confounder in Studies on Hematopoietic Drugs

Analgesic and anesthetic drugs may have an impact on the results achieved from animal experiments. In the study presented here, we try to enlighten whether anesthesia with fentanyl/fluniasone and midazolam (Hypnorm and Dormicum) has an influence on measurements of hemoglobin in mice. In a cross-over study, we have compared hemoglobin levels in two groups of mice: anesthetized versus non-anesthetized and found significant decrease in hemoglobin levels in the anesthetized group (p < 0.05) unrelated to which group received the anesthesia. The mean hemoglobin levels after intraperitoneal administration of Hypnorm and Dormicum was 8.7 mmol/L compared to mean hemoglobin 9.9 mmol/L before anesthesia (p < 0.001), and the decrease lasted for more than 30 min. These results show that anesthesia can be an important confounder in studies involving measurements of hemoglobin, and this should be taken into account when planning studies and analyzing data

An Extended Hypofractionated Palliative Radiotherapy Regimen for Head and Neck Carcinomas

BackgroundPalliative radiotherapy to patients with head and neck cancer is often necessary, but there is a substantial variation in the treatment regimens reported in the literature, and consensus on the most appropriate schedules does not exist. In order to minimize acute toxicity while at the same time trying to achieve prolonged tumor control, a long hypofractionated regimen has been used routinely in Denmark. In the current retrospective study, we investigated the outcome in patients intended for palliative radiotherapy with this regimen.Materials and methodsPatients with newly diagnosed head and neck cancer treated with palliative radiotherapy of 52–56 Gy in 13–14 fractions twice weekly from 2009 to 2014 were included. Patients were excluded if they had previously received radiotherapy. Data on disease location, stage, patient performance status (PS), treatment response, acute skin and mucosal toxicity, and late fibrosis were collected prospectively and supplemented with information from medical records.Results77 patients were included in the study. Fifty-eight patients (75%) completed the intended treatment. Loco-regional tumor response (complete or partial) was evaluated 2 months posttreatment and observed in 45% of the entire population corresponding to 71% of patients alive. PS had a significant influence on survival (p = 0.007) and on not completing the intended treatment. Grade III or IV acute mucositis were observed in 25%, and grade III or IV acute dermatitis observed in 15%.ConclusionPalliative hypofractionated radiotherapy with 52–56 Gy in 13–14 fractions shows good tumor response and tolerability in a vulnerable patient population. However, it may not be suited for patients in poor PS